Cyclic angiotensin-(1-7) contributes to rehabilitation of animal performance in a rat model of cerebral stroke

Peptides. 2020 Jan;123:170193. doi: 10.1016/j.peptides.2019.170193. Epub 2019 Nov 5.

Abstract

Peptidase-resistant, lanthionine-stabilized angiotensin-(1-7), termed cAng-(1-7), has shown therapeutic efficacy in animal models of cardiovascular, metabolic, kidney and pulmonary disease. Goal of the present study was testing the capacity of subcutaneously administered cAng-(1-7) to induce rehabilitation of animal performance in the transient middle cerebral artery occlusion rat model of cerebral stroke. 24 h after ischemic stroke induction, cAng-(1-7) was administered for 28 days at a dose of 500 μg/kg/day, either daily via subcutaneous injection or continuously via an alzet pump. Both ways of administration of cAng-(1-7) were equally effective. Measurements were continued until day 50. Compared to vehicle, cAng-(1-7) clearly demonstrated significantly increased capillary density (p < 0.01) in the affected hemisphere and improved motor and somatosensory functioning. The modified neurological severity score (p < 0.001 at days 15 and 50), stepping test (p < 0.001 at days 36-50), forelimb placement test (p < 0.001 at day 50), body swing test (p < 0.001 at days 43 and 50) all demonstrated that cAng-(1-7) caused significantly improved animal performance. Taken together the data convincingly indicate rehabilitating capacity of subcutaneously injected cAng-(1-7) in cerebral ischemic stroke.

Keywords: Angiotensin-(1-7); Arteries; Brain; Endothelium; Lanthionine; Lanthipeptide.

MeSH terms

  • Angiotensin I / pharmacology*
  • Animals
  • Disease Models, Animal
  • Male
  • Peptide Fragments / pharmacology*
  • Peptides, Cyclic / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects*
  • Stroke Rehabilitation*
  • Stroke* / drug therapy
  • Stroke* / physiopathology

Substances

  • Peptide Fragments
  • Peptides, Cyclic
  • Angiotensin I
  • angiotensin I (1-7)